Novel enantiopure isoxazolidine and C-alkyl imine oxide derivatives as potential hypoglycemic agents: Design, synthesis, dual inhibitors of α-amylase and α-glucosidase, ADMET and molecular docking study

Sep 18, 2020Bioorganic chemistry

New pure forms of isoxazolidine and C-alkyl imine oxide compounds as possible blood sugar-lowering agents: design, creation, dual inhibition of carbohydrate-digesting enzymes, safety, and molecular modeling

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Abstract

Compounds 7b and 7a are identified as potent inhibitors of human pancreatic α-amylase and human lysosomal acid-α-glucosidase, with inhibitory effects up to 9 and 21 times higher than acarbose, respectively.

  • The newly synthesized isoxazolidine and C-alkyl imine oxide derivatives showed higher potency against human pancreatic α-amylase and human lysosomal acid-α-glucosidase compared to acarbose.
  • Compound 7b demonstrated an inhibitory concentration of 23.1 ± 1.1 μM for human pancreatic α-amylase.
  • Compound 7a exhibited an inhibitory concentration of 36.3 ± 1.6 μM for human lysosomal acid-α-glucosidase.
  • Molecular docking studies indicated that compounds 7b and 7a may have stronger interactions with the active sites of the target enzymes.
  • An in silico ADMET profile suggested satisfactory oral druglikeness and absence of toxic effects for both compounds.

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